A Self-Polymerizing Mesh of Nano-Tethers for the Mechanical Constraint of Degraded Intervertebral Discs-A Review of 25 Years of Pre-Clinical and Early Clinical Research.

Genipin polymers are self-forming tensile-load-carrying oligomers, derived from the gardenia fruit, that covalently bond to amines on collagen. The potential therapeutic mechanical benefits of a non-discrete in situ forming mesh of genipin oligomers for degraded spinal discs were first conceived in 1998. Over more than two decades, numerous studies have demonstrated the immediate mechanical effects of this injectable, intra-annular polymeric mesh including an early demonstration of an effect on clinical outcomes for chronic or recurrent discogenic low back pain. This literature review focused on articles investigating mechanical effects in cadaveric animal and human spinal discs, biochemical mechanism of action studies, articles describing the role of mechanical degradation in the pathogenesis of degenerative disc disease, initial clinical outcomes and articles describing current discogenic low back pain treatment algorithms. On the basis of these results, clinical indications that align with the capabilities of this novel injectable polymer-based treatment strategy are discussed. It is intended that this review of a novel nano-scale material-based solution for mechanical deficiencies in biologically limited tissues may provide a helpful example for other innovations in spinal diseases and similarly challenging musculoskeletal disorders.

24-Month Outcomes of Indirect Decompression Using a Minimally Invasive Interspinous Fixation Device versus Standard Open Direct Decompression for Lumbar Spinal Stenosis: A Prospective Comparison.

Purpose: An early-stage, multi-centre, prospective, randomised control trial with five-year follow-up was approved by Health Research Authority to compare the efficacy of a minimally invasive, laterally implanted interspinous fixation device (IFD) to open direct surgical decompression in treating lumbar spinal stenosis (LSS). Two-year results are presented. Patients and Methods: Forty-eight participants were randomly assigned to IFD or decompression. Primary study endpoints included changes from baseline at 8-weeks, 6, 12 and 24-months follow-ups for leg pain (visual analogue scale, VAS), back pain (VAS), disability (Oswestry Disability Index, ODI), LSS physical function (Zurich Claudication Questionnaire), distance walked in five minutes and number of repetitions of sitting-to-standing in one minute. Secondary study endpoints included patient and clinician global impression of change, adverse events, reoperations, operating parameters, and fusion rate. Results: Both treatment groups demonstrated statistically significant improvements in mean leg pain, back pain, ODI disability, LSS physical function, walking distance and sitting-to-standing repetitions compared to baseline over 24 months. Mean reduction of ODI from baseline levels was between 35% and 56% for IFD (p<0.002), and 49% to 55% for decompression (p<0.001) for all follow-up time points. Mean reduction of IFD group leg pain was between 57% and 78% for all time points (p<0.001), with 72% to 94% of participants having at least 30% reduction of leg pain from 8-weeks through 24-months. Walking distance for the IFD group increased from 66% to 94% and sitting-to-standing repetitions increased from 44% to 64% for all follow-up time points. Blood loss was 88% less in the IFD group (p=0.024) and operating time parameters strongly favoured IFD compared to decompression (p<0.001). An 89% fusion rate was assessed in a subset of IFD participants. There were no intraoperative device issues or re-operations in the IFD group, and only one healed and non-symptomatic spinous process fracture observed within 24 months. Conclusion: Despite a low number of participants in the IFD group, the study demonstrated successful two-year safety and clinical outcomes for the IFD with significant operation-related advantages compared to surgical decompression.

Early Clinical Results of Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers.

Background: Genipin is a polymer-forming collagen bonding substance that can be dissolved in a buffered carrier and injected into disc annulus tissues. Therapeutic benefit is derived from the mechanical support provided by a large number of genipin polymers attached to collagen fibers in a degraded disc. Study Design/Setting: IRB-approved prospective, multi-site, single-arm, 12-month feasibility studies were undertaken in two countries to evaluate the safety and efficacy of the genipin-based implant for treating discogenic chronic low back pain (CLBP). Patient Sample: Twenty CLBP patients with symptomatic discs at one or two levels were enrolled in the study. Outcome Measures: The primary safety endpoint was serious adverse events at 1 month, and the primary efficacy endpoint was reduction of pain and disability at 3 months. Secondary efficacy endpoints included reduction of pain and disability at 2 weeks, 1 month, 6 months, and 12 months; reduction of flexion-extension instability; increase in segmental lordosis and rotation; and patient satisfaction. Methods: Fluoroscopic image-guidance was used to deliver two posterolateral injections of buffered genipin to each symptomatic disc. Flexion-extension radiographs were used to quantify joint kinematics at three time-points. Results: Clinically meaningful improvements in pain and disability scores were reported in 80% or more of patients from 2 weeks to 1 year post-treatment. For the more severely unstable joints, treatment significantly reduced the instability score from a pre-treatment level of 2.4 standard deviations above the mean for an asymptomatic population to the asymptomatic mean at the 3-month follow-up. Conclusion: These initial clinical data demonstrate the safety and efficacy of a genipin-based collagen tethering device capable of improving spinal joint stability while successfully addressing CLBP. This work merits additional randomized clinical studies.

Interspinous-Interbody Fusion via a Strictly Lateral Surgical Approach: A Biomechanical Stabilization Comparison to Constructs Requiring Both Lateral and Posterior Approaches.

Objective Lumbar fusion performed through lateral approaches is becoming more common. The interbody devices are generally supported by supplemental posterior fixation implanted through a posterior approach, potentially requiring a second incision and intraoperative repositioning of the patient. A minimally invasive lateral interspinous fixation device may eliminate the need for intraoperative repositioning and avoid disruption of the supraspinous ligament. The objective of this in vitrobiomechanical study was to investigate segmental multidirectional stability and maintenance of foraminal distraction of a lateral interspinous fixation device compared to commonly used pedicle screw and facet screw posterior fixation constructs when combined with lumbar interbody cages. Methods Six human cadaver lumbar spine specimens were subjected to nondestructive quasistatic loading in the following states: (1) intact; (2) interspinous fixation device alone and (3) with lateral interbody cage; (4) lateral lumbar interbody cage with bilateral pedicle screws; (5) lateral lumbar interbody cage with unilateral pedicle screws; and (6) lateral lumbar interbody cage with facet screws. Multidirectional pure bending in 1.5 Nm increments to 7.5 Nm, and 7.5 Nm flexion-extension bending with a 700 N compressive follower load were performed separately with optoelectronic segmental motion measurement. Relative angular motions of L2-L3, L3-L4, and L4-L5 functional spinal units were evaluated, and the mean instantaneous axis of rotation in the sagittal plane was calculated for the index level. Foraminal height was assessed during combined flexion-extension and compression loading for each test construct. Results All implant configurations significantly restricted flexion-extension motion compared with intact (p < 0.05). No significant differences were found in flexion-extension when comparing the different posterior implants combined with lateral lumbar interbody cages. All posterior fixation devices provided comparable neuroforaminal distraction and maintained distraction during flexion and extension. Conclusions When combinedwith lateral lumbar interbody cages, the minimally invasive lateral interspinous fixation device effectively stabilized the spine and maintained neuroforaminal distraction comparable to pedicle screw constructs or facet screws. These results suggest the lateral interspinous fixation device may provide a favorable alternative to other posterior systems that require patient repositioning during surgery and involve a greater disruption of native tissues.

Instrumented Posterior Arthrodesis of the Lumbar Spine: Prospective Study Evaluating Fusion Outcomes in Patients Receiving an Interspinous Fixation Device for the Treatment of Degenerative Spine Diseases.

Purpose: Prospective evaluation of radiographic fusion outcomes in patients receiving instrumented posterior arthrodesis of the lumbar spine using a minimally invasive interspinous fixation device. Patients and Methods: All patients (n = 110) from a single US physician's practice who received instrumented posterior arthrodesis of the lumbar spine with a minimally invasive interspinous fixation device in the calendar year 2020 were invited to return for a follow-up CT scan to radiographically assess fusion. Forty-three patients, representing 69 total treated levels, consented to participate and received a lumbar CT scan at a mean of 459 days post-surgery (177 to 652). The interspinous/interlaminar fusion was assessed by 3 independent radiologists using a novel grading scale. Spinous process fractures were also assessed. Results: 92.8% of the assessed levels were considered fused. There were no intraoperative spinous process fractures. There were 4 spinous process fractures (5.8%) identified on CT imaging, all of which were asymptomatic and healed without subsequent intervention. There were no instances of device mechanical failure or device-related reoperation. Conclusion: Instrumented posterior arthrodesis of the lumbar spine using a minimally invasive interspinous fixation device provides clinically meaningful fusion rates with no reoperations and a low risk of spinous process fracture or other device-related complications.

Soft Palate Modification Using a Collagen Crosslinking Reagent for Equine Dorsal Displacement of the Soft Palate and Other Upper Airway Breathing Disorders.

The mechanical properties of the soft palate can be associated with breathing abnormalities. Dorsal displacement of the soft palate (DDSP) is a naturally occurring equine soft palate disorder caused by displacement of the caudal edge of the soft palate. Snoring and a more serious, sometimes life-threatening, condition called obstructive sleep apnea (OSA) are forms of sleep-related breathing disorders in humans which may involve the soft palate. The goal of this study was to investigate the effect of injecting the protein crosslinker genipin into the soft palate to modify its mechanical properties for the treatment of equine DDSP with potential implications for the treatment of snoring and OSA in humans. Ex vivo experiments consisted of mechanical testing and a wind tunnel study to examine the effect of genipin on the mechanical properties, displacement, and vibration of equine soft palates. A pilot in vivo study was completed using DDSP and control horses to test the safety and effectiveness of injecting a genipin reagent into the soft palate. The wind tunnel testing demonstrated a greater than 50% decrease in transient deformation and a greater than 33% decrease in steady-state vibrations for all doses of genipin tested. Ultimate tensile stress, yield stress, and Young's modulus were higher in the genipin-treated distal soft palate specimens by 52%, 53%, and 63%, respectively. The pilot in vivo study showed a reduction of snoring loudness in all DDSP horses and elimination of DDSP in at least one of three horses. The difficulty of using a 1-meter-long endoscopic injection needle contributed to a consistent overinjection of the equine soft palates, causing excessive stretching (pillowing) and related degradation of the tissue. These ex vivo and in vivo results demonstrated reduced vibration amplitude and flaccidity and increased strength of genipin-treated soft palates, suggesting that genipin crosslinking could become an effective and safe treatment for soft palate related breathing abnormalities.

Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue.

The most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid-release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid-release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull-out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199-2205, 2017.

Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs.

Exogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.

Exogenous Crosslinking Restores Intradiscal Pressure of Injured Porcine Intervertebral Discs: An In Vivo Examination Using Quantitative Discomanometry.

STUDY DESIGN: In vivo examination of intradiscal pressure by quantitative discomanometry (QD). OBJECTIVE: To determine whether an injectable, exogenous crosslinking could acutely restore intradiscal pressure of stab-injured discs in vivo by short-term treatment. SUMMARY OF BACKGROUND DATA: Disc biomechanical performance depends on its integrity associated with the intradiscal pressure and mechanical properties. Genipin crosslink augmentation has demonstrated the in vitro biomechanical capability to improve intervertebral joint stability and increase mechanical properties of the annulus fibrosus. METHODS: 4 lumbar discs on each of 8 swine were randomly assigned to 4 groups: intact, injured, untreated, and crosslinked. A 16G needle was stabbed into the annulus fibrosus to create the disc injury model. An injection of 0.33% genipin solution was delivered into the annulus to treat the injury. QD technique was performed to examine the intradiscal pressure for the intact and injured discs at the time of surgery, while untreated and crosslinked discs were measured 1-week postsurgery. 4 QD parameters were analyzed and compared across the 4 groups: leakage pressure and volume, and saturation pressure and volume. RESULTS: The leakage and saturation pressures of the injured group were significantly lower than those of the intact group (P = 0.004 and P = 0.01, respectively). The leakage and saturation pressures of untreated discs were statistically equivalent to the injured levels, but with a 2-times higher saturation volume. Relative to the untreated group, the leakage pressure and saturation pressure of genipin-crosslinked discs had a 617% (P = 0.008) and a 473% increase (P = 0.007), respectively. CONCLUSION: A large disc injury produced by annular puncture immediately lowered intradiscal pressure when left untreated. Genipin crosslinking can restore intradiscal pressure acutely in vivo without any obvious morbidity associated with the injection.

Changes in the interfacial shear resistance of disc annulus fibrosus from genipin crosslinking.

Crosslinking soft tissue has become more common in tissue engineering applications, and recent studies have demonstrated that soft tissue mechanical behavior can be directly altered through crosslinking. Using a recently reported test method that shears adjacent disc lamella, the effect of genipin crosslinking on interlamellar shear resistance was studied using in vitro bovine disc annulus. Specimens of adjacent lamella were dissected from four discs taken from three fresh frozen bovine tails. These specimens were paired and soaked in either 50 mM EPPS Phosphate (ph9) with 20 mM genipin at 37 °C for 4 h or in 50 mM EPPS Phosphate (ph9) of which twelve specimens (6 per treatment) were successfully tested and analyzed. Crosslinked specimens were noted to have significantly higher yield force per width (59%), peak force per width (70%), and resilience (69%) compared to sham treated controls, supporting the hypothesis that genipin crosslinking increases the resistance to interlamellar shear of the annulus interface. Additionally, a possible dependency may exist between the interlamellar shear strength and neighboring lamella because of the bridging fiber network previously described by other investigators.

The dose response relationship between intervertebral disc flexion-extension neutral zone metrics and injected genipin concentration.

PURPOSE: Quantify changes in the flexion--extension neutral zone of the intervertebral disc with injections of increasing genipin concentration. METHODS: Bovine motion segments were treated with varying concentrations of genipin using bilateral injections of constant volume. After overnight static compression loading of the treated segments, anterior-posterior offset loading was used to simulate flexion-extension motion. Range of motion, neutral zone length, neutral zone stiffness, and an instability score were measured. RESULTS: Injection of the disc annulus with increasing concentrations of genipin resulted in corresponding changes in flexion-extension neutral zone. A minimum concentration of 40 mM was needed to observe a significant change. The largest changes were observed with the 400 mM injection. Netural zone stability was the most sensitive of the metrics with a percent change of 48% at 40 mM and over 200% at 400 mM. CONCLUSION: This study establishes the efficacy of using injection delivery to affect disc joint mechanics and quantifies the dose response between injected genipin and the flexion-extension stability of the disc.

Lumbar facet joint and intervertebral disc loading during simulated pelvic obliquity.

BACKGROUND CONTEXT: Intervertebral disc and facet joints are the two primary load-bearing structures of the lumbar spine, and altered loading to these structures may be associated with frontal plane spinal deviations. PURPOSE: To determine the load on the lumbar facet joint and intervertebral disc under simulated frontal plane pelvic obliquity combined loading, an in vitro biomechanical study was conducted. STUDY DESIGN/SETTING: An in vitro biomechanical study using a repeated-measures design was used to compare L4-L5 facet joint and intervertebral disc loading across pure moment and combined loading conditions. METHODS: Eight fresh-frozen lumbosacral specimens were tested under five loading conditions: flexion/extension, lateral bending, axial rotation using pure moment bending (±10 Nm), and two additional tests investigating frontal plane pelvic obliquity and axial rotation (sacrum tilted left 5° and at 10° followed by a ±10-Nm rotation moment). Three-dimensional kinematics, facet load, and intradiscal pressures were recorded from the L4-L5 functional spinal unit. RESULTS: Sagittal and frontal plane loading resulted in significantly smaller facet joint forces compared with conditions implementing a rotation moment (p<.05). The facet joint had the highest peak load during the 10° combined loading condition (124.0±30.2 N) and the lowest peak load in flexion (26.8±16.1 N). Intradiscal pressure was high in lateral flexion (495.6±280.9 kPa) and flexion (429.0±212.9 kPa), whereas intradiscal pressures measured in rotation (253.2±135.0 kPa) and 5° and 10° combined loading conditions were low (255.5±132.7 and 267.1±127.1 kPa, respectively). CONCLUSIONS: Facet loading increased during simulated pelvic obliquity in frontal and transverse planes, whereas intradiscal pressures were decreased compared with sagittal and frontal plane motions alone. Altered spinopelvic alignment may increase the loads experienced by spinal tissue, especially the facet joints.

Exogenous collagen crosslinking of the intervertebral disc restores joint stability after lumbar posterior decompression surgery.

STUDY DESIGN: In vitro evaluation of a chemical, injectable intervention for discectomy induced destabilization. OBJECTIVE: To investigate the ability of two collagen crosslinking agents to restore mechanical properties to lumbar joints destabilized by surgical decompression procedures. SUMMARY OF BACKGROUND DATA: Posterior decompression surgery is a common procedure indicated for tissue pathology that interferes with surrounding neural structures. Previous in vitro, analytical, and clinical studies have shown that removal of load-supporting tissue can compromise joint stability mandating some form of postsurgical stabilization. Currently, no nonsurgical treatments are capable of restoring stability and preventing subsequent degeneration. Exogenous crosslinking of intact discs has shown a fourfold increase in joint stability. METHODS: Fifteen bovine lumbar intervertebral joints were randomly separated into methylglyoxal or genipin treatment groups. Flexion-extension flexibility was quantified in three conditions: intact, postdecompression surgery, and after crosslinking reagent injections. Instability was quantified by calculating neutral zone (NZ), percentage of hysteresis, range of motion, and percentage of strain energy. RESULTS: Simulated surgical decompression increased NZ 111% (P = 0.009), 28% (P = 0.004), range of motion 57% (P = 0.003), and decreased strain energy 37% (P = 0.004). For those discs undergoing methylglyoxal treatment NZ was subsequently reduced 68% (P = 0.012), hysteresis 28% (P = 0.018), range of motion 29% (P = 0.012), and strain energy was increased 71% (P = 0.018). For discs subjected to genipin treatment, NZ was reduced 52% (P = 0.018), hysteresis 23% (P = 0.012), range of motion 44% (P = 0.017), and strain energy was increased 66% (P = 0.012). Mean NZ was lower than intact mean after both methylglyoxal and genipin treatments, 10% and 17% less, respectively, but these differences were not significant. Mean values for all other parameters posttreatment were within 6% of the corresponding intact mean values. CONCLUSION: Injections of crosslinking reagents into lumbar intervertebral discs after simulated decompression surgery restored joint stability according to all parameters. Similar results were found for genipin and methylglyoxal reagents. Implementing exogenous collagen crosslinking as an adjunct to current surgical decompression procedures may be beneficial in preventing or delaying subsequent spinal instability and degeneration.

The effects of exogenous crosslinking on hydration and fluid flow in the intervertebral disc subjected to compressive creep loading and unloading.

STUDY DESIGN: In vitro study of genipin crosslinking effect on disc water content changes under compressive loading and unloading. OBJECTIVE: To investigate the influence of collagen crosslinking on hydration and fluid flow in different regions of intact discs, and to evaluate the nutritional implications. SUMMARY OF BACKGROUND DATA: Age-related reductions of nutrient supply and waste product removal are critically important factors in disc pathogenesis. Diffusion and fluid flow are blocked by subchondral bone thickening, cartilaginous endplate calcification, loss of hydrophilic proteoglycans, and clogging of anular pores by degraded matrix molecules. Previous studies demonstrated increased hydraulic permeability and macromolecular transport through crosslinked collagenous matrices. Genipin has also demonstrated the capability to increase retention of proteoglycans. METHODS: A total of 57 bovine lumbar motion segments were divided randomly into phosphate buffered saline and 0.33% genipin-soaked treatment groups. Water content changes were measured using a mass-loss technique in 3 intervertebral disc regions following successive stages of compressive loading and unloading (post-treatment, after 1 hour 750 N compression, and after a subsequent 24-hour period of nominal loading). Net flow of fluid into or out of a region was determined from the percentage change in mean water content from successive groups. RESULTS: Fluid flow to and from the nucleus doubled with genipin crosslinking. Relative to the buffer-only controls, overall net fluid flow increased 103% in the nucleus pulposus, 36% in the inner anulus, and was 31% less in the outer anulus of genipin treated discs. CONCLUSION: The effects of genipin crosslinking on matrix permeability and proteoglycan retention can alter hydration levels and fluid flow in the intervertebral disc. Resulting increases in fluid flow, including a doubling of flow to and from the nucleus, could lead to enhanced nutritional inflow and waste product outflow for the disc, and may have implications for emerging cell-based therapies.

Sterilization effects on the mechanical properties of human bone-patellar tendon-bone allografts.

Novel allograft processing methods are available from tissue banks to decrease disease transmission. This study evaluated the effects of 3 of these techniques on the initial mechanical properties of bone-patellar tendon-bone (BPTB) allografts: (1) aseptic harvest with low-dose radiation processing, (2) BioCleanse Tissue Processing System, and (3) Clearant Process. Ten-mm BPTB allografts were potted in an MTS 858 machine (MTS Systems Corp, Eden Prairie, Minnesota), cycled, and loaded to failure at a strain rate of 100%/s. Data were critically analyzed for graft dimensions and age and sex of donor. The 10th cycle and last cycle stiffness after 1000 cycles were measured at the toe region and at all points. The 2% yield stress (MPa), Young's modulus (MPa), elongation failure (mm), strain fracture (%), ultimate stress (MPa), and toughness (kJ) were measured. Forty-two tendons were tested (15 control, 11 BioCleanse, and 16 Clearant). No statistically significant differences were detected between the groups at their 10th cycle and last cycle stiffness (P>.05). Yield stress ranged from 19 to 28.8 MPa without a statistically significant difference (P>.05). Young's modulus ranged from 178.3 to 213.8 MPa without a statistically significant difference (P>.05). Similarly, elongation to failure, strain to failure, ultimate stress, and toughness showed no statistically significant differences among the 3 groups (P>.05). These processing techniques did not affect the time zero mechanical properties of the BPTB allograft tendons under these testing conditions. Clinical use of allografts should proceed with caution for selected patients.

The influence of exogenous cross-linking and compressive creep loading on intradiscal pressure.

This study involves a biomechanical evaluation of a prospective injectable treatment for degenerative discs. The high osmolarity of the non-degenerated nucleus pulposus attracts water contributing to the hydrostatic behavior of the tissue. This intradiscal pressure is known to drop as fluid is exuded from the matrix due to compressive loading. The objective of this study was to compare the changes in intradiscal pressure in control and genipin cross-linked intervertebral discs. Thirty bovine lumbar motion segments were randomly divided into a phosphate-buffered saline control group and a 0.33% genipin group and soaked at room temperature for 2 days. A needle pressure sensor was held in the center of the disc while short-term and static creep compressive loads were applied. The control group demonstrated a 25% higher average intradiscal pressure compared to genipin-treated discs under 750 N compressive load (p=0.029). Depressurization during static compressive creep was 56% higher in the control than in the genipin group (p=0.014). These results suggest cross-linking induced changes in the poroelastic properties of the involved tissues affected the mechanics of compressive load support in the disc with lower levels of nucleus pressure, a corresponding decrease in the elastic expansion of the annulus, and an increased axial compressive loading of the inner and outer annulus tissues. It is possible that concurrent changes in hydraulic permeability and proteoglycan retention known to be associated with genipin cross-linking were also contributors to poroelastic changes. Reduction of peak pressures and moderation of pressure fluctuations could be beneficial relative to discogenic pain.

The analysis of axisymmetric viscoelasticity, time-dependent recovery, and hydration in rat tail intervertebral discs by radial compression test.

The goal of this study was to develop a nondestructive radial compression technique and to investigate the viscoelastic behavior of the rat tail disc under repeated radial compression. Rat tail intervertebral disc underwent radial compression relaxation testing and creep testing using a custom-made gravitational creep machine. The axisymmetric viscoelasticity and time-dependent recovery were determined. Different levels of hydration (with or without normal saline spray) were supplied to evaluate the effect of changes in viscoelastic properties. Viscoelasticity was found to be axisymmetric in rat-tail intervertebral discs at four equidistant locations. Complete relaxation recovery was found to take 20 min, whereas creep recovery required 25 min. Hydration was required for obtaining viscoelastic axisymmetry and complete viscoelastic recovery.

Effects of exogenous crosslinking on in vitro tensile and compressive moduli of lumbar intervertebral discs.

BACKGROUND: Collagen crosslinks may play a vital role in preventing ongoing disc degeneration. Age-accumulating crosslinks have been thought to increase brittleness and reduce fatigue resistance. However recent studies have demonstrated increases in fatigue resistance, joint stability and nutritional flow properties resulting from crosslink augmentation. In this study, multi-directional moduli of bovine lumbar intervertebral discs were measured in vitro, including circumferential tension, radial compression, axial tension, and axial compression in control and crosslinked specimens. METHODS: Four types of annulus fibrosus specimens were dissected from control and crosslinked discs. Cross-sectional areas were measured using a non-contact laser measurement system and then four separate mechanical tests were conducted using a materials testing machine with custom-made loading fixtures. FINDINGS: The circumferential specimens demonstrated the highest moduli in both low stiffness and linear elastic regions. After a crosslink treatment, the modulus increased more in circumferential tension compared to axial tension and more in axial compression compared to radial compression. Other tensile properties had higher increases in circumferential tension compared to axial tension after crosslinking. INTERPRETATION: Assuming form follows function, circumferential tension is the predominant type of stress experienced by non-degenerated annulus fibrosus. The anisotropic mechanical properties of the annulus fibrosus is non-uniformly affected by crosslink augmentation. Dominant effects were in the directions with greater inherent stiffnesses. These results suggest some beneficial effects of crosslink augmentation on the mechanical properties of the annulus fibrosus: increase in ultimate strength, yield strength, toughness, and modulus in the principal stress directions.

Exogenous cross-linking increases the stability of spinal motion segments.

STUDY DESIGN: The mechanical stability of cross-linked and control spinal motion segments was evaluated using neutral zone, range of motion (ROM), and instability score metrics. OBJECTIVE: To determine if exogenous cross-linking could increase the stability of spinal motion segments. SUMMARY OF BACKGROUND DATA: The microstructure of the anulus fibrosus extracellular matrix can affect the stability of the intervertebral joint. Parallel testing in our laboratory has shown that exogenous cross-linking can improve the fatigue resistance of anulus fibrosus. METHODS: There were 3 separate experimental protocols conducted. The first study used calf lumbar intervertebral joints randomly divided into a genipin cross-linked group and phosphate buffered saline-soaked controls. After 2 days of soaking, flexion-extension ramp cycles were applied to the specimens. The second study repeated the test protocol using 22 moderately and severely degenerated human lumbar intervertebral joints. The third experiment compared the effect of cross-linking treatment on human discs with known degrees of preexisting mechanical instability. Each data set was used to assess joint instability by 3 calculations: ROM, neutral zone, and an instability score. Joint instability for each data set was evaluated using 3 calculations: ROM, neutral zone, and a novel instability score. RESULTS: These results show that cross-link augmentation can effectively reduce instability of intervertebral discs. The stabilizing effect was observed to be higher in the more mechanically unstable discs. However, cross-linking did not appear to affect the total range of sagittal motion. CONCLUSIONS: By reducing the neutral zone, exogenous cross-linking may help combat the progression of instability in degenerative disc disease.

Stability provided by the sternum and rib cage in the thoracic spine.

STUDY DESIGN: Multidirectional flexibility tests were conducted on 10 human thoracic spines with intact rib cage. OBJECTIVES: To determine the amount of stability the rib cage imparts to the thoracic spine and to show the amount of stability lost by a sternal fracture. SUMMARY OF BACKGROUND DATA: There is no published study of biomechanical testing of human cadaveric specimens with the rib cage intact. METHODS: In this study, 10 human cadaveric thoracic spines with the rib cage intact were tested using a biaxial material testing machine and an opto-electronic three-dimensional motion measuring device (Opto-trak 3020). The specimens were tested in axial compression, axial rotation, lateral bending, and flexion/extension. First, the specimens were tested through all four loading types with the sternum and rib cage intact. Next, the sternum was fractured at the sternomanubrial junction displacing the proximal fragment posteriorly. Lastly, the entire rib cage was removed. RESULTS: The rib cage increased the stability of the thoracic spine by 40% in flexion/extension (P = 0.012), 35% in lateral bending (P = 0.008), and 31% in axial rotation (P = 0.008). An indirect flexion-compression type of sternal fracture decreased the stability of the thoracic spine by 42% in flexion/extension (P = 0.036), 22% in lateral bending (P = 0.038), and 15% in axial rotation (P = 0.011). CONCLUSION: The rib cage significantly increases the stability of the thoracic spine in flexion/extension, lateral bending, and axial rotation. A sternal fracture significantly decreases the stability of the thorax.